Potassium hexamethyldisilazide KHMDS

Azatriquinadiene (2,3-dihydroazatriquinacene) 39 has been efficiently synthesized from enamine 389. Enamine 389 on treatment with bromine followed by aqueous work-up afforded the tetrabromohemiaminal 390. Dehydrohalogenation of 390 with potassium hexamethyldisilazide (KHMDS) and compound 391 on reduction with lithium aluminium hydride yielded the target molecule azatriquinadiene 39 in good overall yield (Scheme 85) <2000JOC7253>. 

The phosphorylated bromobenzamide derivative 180 cyclizes to produce the phosphorylated isoindolinone on exposure to an excess of potassium hexamethyldisilazide (KHMDS) (Equation 116) <2000T1491>. 

The most widely used method for the preparation of free NHCs is the deprotonation of an azohum salt with NaH or KOBuf [10,14,37]. In the case of N,N -methylene-bridgcd bisimidazolium salts, the preparation of the free dicarbenes is only possible by the use of potassium hexamethyldisilazide (KHMDS) in toluene [14,41]. Other strong bases deprotonate the methylene bridge breaking the bisazol unit [42],... 

This asymmetric induction is strongly affected by the base. Asymmetric methylation of 32 occurred with retention of configuration when lithium 2,2,6,6-tetramethylpiperidide (LTMP) or LDA was used, while inversion of configuration was observed with potassium hexamethyldisilazide (KHMDS)... 

NPf) protected amine. The final ring formation was carried out by deprotonation of the benzylic methyl with potassium hexamethyldisilazide (KHMDS) which then added to the methyl ester to provide ketone 316. This compound was then carried on through a series of transformations to provide a common intermediate for every member of the FR900482 family. 

Crown-6 (3.51 g, 13.28 mmol) was taken in 30 mL of THF, and the flask was cooled to -78 °C before addition of the phosphonate (2.90, 8.38 mmol) followed by dropwise addition of potassium hexamethyldisilazide (KHMDS 0.5 M in toluene, 16.0 mL, 8.38 mmol). After 10 min, the aldehyde (1.59 g, 6.68 mmol) was added in THF (10 mL). The reaction was quenched after 5 min with Nal ICO , solution. Extractive workup with methyl fert-butyl ether followed. The organic layer was then dried over MgSO4 and filtered. The solvent was evaporated in vacuo, and the crude product was chromatographed (hexane/EtOAc, 3 1) to give 1.73 g (85%) of the (Z)-a,p-unsaturated ethyl ester. 

Recently, the ability of N-heterocyclic carbenes to promote the Staudinger reaction has been investigated using ionic liquids, in the presence of suitable base as pre-catalysts. According to the procedure suggested by Smith et al., a solution of base (potassium hexamethyldisilazide KHMDS, toluene as solvent) was added to the suspension of ionic liquid (triazolium salt) in Et O and stirred under N. Subsequently, the mixture was added of diphenylketene and of imine and stirred at room temperature before concentration in vacuo (Scheme 16.6). The order of addition of reactants is critical for the success of the synthesis [95]. 

Subsequently, the ability of enantiomerically pure N-heterocyclic carbenes (NHCs) to catalyse the enantioselective Staudinger reaction has been tested. Different NHCs, obtained via deprotonation by potassium hexamethyldisilazide KHMDS in Et O of the respective parent ionic liquids, are able to promote the cycloaddition of diphenylketene and N-tosylimide giving P-lactams in elevated yields and 55-75% e.e. (Scheme 16.7) [95]. 

An alternative approach to alkylidene carbenes uses the deprotonation or halogen-lithium exchange of vinyl haUdes. Hence, treatment of the vinyl chloride 103 with potassium hexamethyldisilazide (KHMDS) resulted in the formation of the cyclopentene 104 via the intermediate alkylidene carhene (4.83). The carbene... 

Potassium hexamethyldisilazide, KHMDS, has been used successfully in the past for a-deprotonation of sulfoxides. Aiming to probe the nature of the transition state in the reaction of a-metalated (i )-methyl //-tolyl sulfoxide with A -(benzylidene) aniline under kinetic conditions, the effect of the choice of the bases for the a-deprotonation on the reactivity and diastereoselectivity was studied, using LDA, LHMDS, NaHMDS, and KHMDS. Best yields anddiastereoselectivities (90%, 84 16) were achieved with LDA, whereas LHMDS showed diminished reactivity (50%) without a loss of diastereoselectivity (87 13). Improved yields and lower diastereoselectivities were recorded in reactions mediated by NaHMDS and KHMDS, providing the amine in 60% (dr 81 19) and 77% (dr 69 31) yields and diastereoselectivities, respectively (eq 64). 

The Julia reaction is remarkably versatile but it does need three steps to make the alkene addition, acylation, and reduction. A more recent version of the reaction cuts this down to one by using not a phenylsulfone but instead a sulfone carrying an electron-deficient heterocycle, for example a tetrazole. The anion of the sulfone is made with a strong base (here potassium hexamethyldisilazide, KHMDS—see p. 635) and is added to an aldehyde to give an alkene directly. 

The first DKR of a-aminoaldehydes was reported by Reiser s group who treated aldehydes 1-3 (Scheme 1.42) with chiral phosphonates in the presence of a slight excess of base such as potassium hexamethyldisilazide (KHMDS). According to the nature of the phosphonate, the E- or the Z-product was selectively obtained (Scheme 1.42, Table 1.1)." ... 

The most general protocol (eq 10) has therefore been based on potassium hexamethyldisilazide (KHMDS) as the base addition of trisyl azide at —78 °C and then acetic acid at the same temperature. Excellent levels of diastereoselectivity are ohsCTved with most substrates and the method has been used widely in the enantioselective synthesis of a-amino acids from chiral iniides. Chemoselective azidation of an imide enolate in the presence of an ester function has been demonstrated (eq 11). The product distribution is nevertheless finely balanced, as discovered with the respective dimethyl and dihenzyl ethers of the 3,5-substituted phenylacetyl imide (3) (eq 12). ... 

Bisorbibutenohde (or bislongiquinoUde) (211), a member of sorbidUn-related natural products, is a biosynthetic product of bisorbidUinol (209), as it was reported in 1999 by Nicolaou et al. [113] in his inspiring work on this dass of compounds. On the basis of biosynthetic considerations, Nicolaou converted 209 to 211 on treatment with potassium hexamethyldisilazide (KHMDS) in 80% yield (Scheme 1.33). Later in 2005, Deng et al. [114] prepared optically pure... 

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